1. Field of the Invention
The present invention relates to crystalline forms of a thiazolidinedione compound having a significant ability of peroxisome proliferator-activated receptor (PPAR) γ activation, a significant anticancer activity and favorable properties for manufacturing medicaments, as well as being highly pure and excellent in preservation stability and handleability, manufacturing methods thereof, and medicines containing as an active component the crystalline forms of the thiazolidinedione compound (in particular, PPARγ activators or anticancer pharmaceutical compositions).
2. Description of the Related Art
Japanese Patent No. 3488099 (International Patent Application Laid-Open No. 99/18081, U.S. Pat. No; 6,432,993, European Patent No. 1022272) (Patent Literature 1), Japanese Patent Laid-Open No. 2003-238406 (International Patent Application Laid-Open No. WO03/053440) (Patent Literature 2), Japanese Patent Laid-Open No. 2004-083574 (WO2004/000356) (Patent Literature 3), Japanese Patent Laid-Open No. 2005-162727 (WO2004/083167) (Patent Literature 4), and International Patent Application Laid-Open No. 2007/091622 (Patent Literature 5) disclose a thiazolidinedione compound represented by the after-mentioned formula (I) (abbreviated as Compound (I) hereinafter.). Compound (I) has a significant ability of peroxisome proliferator-activated receptor (PPAR) γ activation and is expected to exert its availability as a PPARγ activator or an anticancer pharmaceutical composition.
In general, substances used in pharmaceutical products are required to have high purity to avoid unexpected adverse effects caused by impurities of the substances. The impurities include by-products (analog substances) being produced during the manufacture of the pharmaceutical ingredients themselves, raw materials and solvents being used for manufacturing the pharmaceutical ingredients and the like. Also, the substances are required to have more favorable physical and chemical properties for manufacturing medicaments such as crystal forms of pharmaceutical ingredients which are resistant to a heat treatment step and the like for preparation, or high solubility which makes pharmaceutical ingredients able to increase their absorbability so that they can exert their effects at lower doses. Moreover, it is important that the pharmaceutical ingredients can be stored for long periods of time, while maintaining the quality. In addition, large-scale refrigerating installations are needed to maintain the quality of pharmaceutical ingredients if they are required to be stored at low temperatures. Therefore, it is industrially significant to find crystalline forms which are stable and such as can be stored at room temperature or even higher temperatures.
As mentioned above, an industrial and large-scale manufacturing method is required to manufacture pharmaceutical ingredients being more highly pure, having favorable properties for manufacturing medicaments and being stockable while stably maintaining their purity and properties for long periods of time.    [Patent Literature 1] Japanese Patent No. 3488099 (Pamphlet of International Patent Application Laid-Open No. 99/18081, Specification of U.S. Pat. No. 6,432,993, Specification of European Patent No. 1022272)    [Patent Literature 2] Japanese Patent Laid-Open No. 2003-238406 (Pamphlet of International Patent Application Laid-Open No. WO03/053440)    [Patent Literature 3] Japanese Patent Laid-Open No. 2004-083574 (Pamphlet No. WO2004/000356)    [Patent Literature 4] Japanese Patent Laid-Open No. 2005-162727 (Pamphlet No. WO2004/083167)    [Patent Literature 5] Pamphlet of International Patent Application Laid-Open No. 2007/091622
The present inventors have done earnest research on Compound (I) which has a significant ability of peroxisome proliferator-activated receptor (PPAR) γ activation and is expected to exert its availability as a PPAR γ activator or an anticancer pharmaceutical composition. As a result, the inventors found novel crystalline forms of hydrates of the dihydrochloride of Compound (I) having significant physical and chemical properties as pharmaceutical ingredients, being excellent in preservation stability at room temperature as well as being highly pure, and manufacturing methods thereof. Based on this finding, the inventors have achieved the present invention.